Bioinorganic chemistry has a cross disciplinary approach, applying the principles of chemistry to biological systems. Metallochemistry of Neurodegeneration: Biological, Chemical and Genetic Aspects discusses the rapidly developing area of metals in the nervous system and their role in neurodegenerative disease, such as Alzheimer’s, Parkinson’s and prion diseases. Written by leading experts in their fields, each chapter combines elements of genetics, biochemistry and biological inorganic chemistry in its discussion. The book highlights the differences in pathologies of neurodegenerative diseases but also discusses the mechanistic similarities. Sections include: metal ions and prion diseases; metal ions and Alzheimer disease; manganese in brain functioning; metal involvement in Parkinson disease; Cu-Zn superoxide dismutase and familial amyotrophic lateral sclerosis. This book will appeal to both chemists and biologists at the post graduate and research level.
Spis treści
I: Introduction; 1:General model for protein misfolding, aggregation, amyloid formation and neurodegeneration; 2: Specificity of molecular mechanisms in major neurodegenerative diseases; Alzheimer disease (AD); Parkinson Disease; Amyotrophic lateral sclerosis; Prions diseases; 3: Models of amyloid seeding in neurodegenerative diseases; References; II: Blood- Brain Barrier and roots of entry of metal ions into the brain. Metal transport and distribution in the brain; 1: General features of blood-brain barrier; 2: Iron and aluminium; 3: Manganese; 4: Lead and mercury; 5: The olfactory pathway of metal entry into the brain; 6: Astroglia and metal accumulation; References; III: Metal ion induced redox reactions, oxidative stress and possible impact on Neurodegeneration; 1: Metal induced production of ROS; 2: Nitric oxide; 3: Oxidative stress and aging; 4: ROS, protein oxidation and aberrant protein interactions; 5: Peroxidation of lipids in aging brain; 6: Impact of oxidative stress on DNA; 7: ROS and cell death; References; IV: Copper Metabolism in the Brain; 1: Introduction; 2: Models of Copper Metabolism; 3: Mammalian Copper Homeostasis; 4: Mammalian Cellular Copper Metabolism; 5: Neurodegenerative diseases and Copper; 6: Wilson and Menkes Diseases; 7: Familial Amyotrophic Lateral Sclerosis (FALS); 8: Conclusions; References; V: Lithium, a neuroprotective element; IMPase; GSK-3; References; VI: Neurotoxicity of aluminium; 1: Neurochemistry of Aluminum; 2: Aluminum and the etiology of Alzheimer’s Disease (AD); References; VII: Manganese in the brain functioning; 1: Introduction; 2: Manganese Absorption; 3: Manganese Transport to the Brain; 4: Manganese Uptake in the Brain; 5: Proteins that Utilise Manganese; 6: Manganese Neurotoxicity; 7: Effects on Brain Function; 8: Neurological Disease related to Manganese; 9 : Conclusions ; References; VIII: Alzheimer’s disease: which metal now?; 1: Amyloid Precursor Protein; 2: Cleavage of APP and formation of ?-Amyloid; 3: Neurofibrillary Tangles; 4: Copper, APP and A?; 5: Metals and Alzheimer’s Disease; 6: A balance between copper and zinc; 7: The rise of iron; 8: Any more metals in Alzheimer’s disease; 9: Coordination chemistry of metal ions interacting with APP; References; IX: Prion diseases and and redox active metal; 1: Introduction; 2: Cu binding to Pr Pc; 3: Details of copper(II) co-ordination to mammalian Pr PC and its fragments; Binding of Cu(II) ion by a single octapeptide repeat Pro-His-Gly-Gly-Gly-Trp-Gly-Gln; p H-dependence of Cu2+ binding to octapeptide fragment; Binding of Cu2+ ions to dimeric and tetrameric octapeptide fragments; 4: The Fifth and Sixth Binding Sites Located in N-Terminal Domain; 5: Binding of Cu(II) and other metals to Pr P91-126 region; Cu(II) coordination to Pr P106-126 (KTNMKHMAGAAAAGAVVGGLG); Involvement of His-96 in the interaction of Cu(II) with the neurotoxic peptide fragment; The comparison of the binding abilities of octameric and neurotoxic regions towards Cu2+ ions; 6: Cu2+ coordination to chicken Pr P; 7: Copper Mediated Pr P Internalisation; 8: Copper Transport; 9: Pr P as an Antioxidant; 10: Manganese Binding; 11: Cell Death and Metals; 12: Metal Changes in TSEs; 13: Copper and Mutant Prions; 14: Conclusions; References; X: Are Metals Involved in Cu-Zn Superoxide Dismutase Related Familial Amyotrophic Lateral Sclerosis; References; XI: Parkinson disease: any role for metals; 1: Introduction; 2: Cell Death in Parkinson’s Disease; 3: Genetics of Parkison’s Disease; 4: The Proteins Associated with Parkinson’s Disease; Parkin; ?-Synuclein; 5: Metals in Parkinson’s Disease; 6: Bioinorganic chemistry in Parkinson disease; Binding of copper ions to ?-synuclein and its fragments; 7: Metal ions and catecholamines; 8: The neuromelanin of substantia nigra and metal ions; 9: Conclusions; References; XII: Chelating Agents in Metal Neurotoxicity; Copper; Lead; Mercury; Iron; References; XIII: Metal Complexes in the Brain Imaging and Diagnosis; Gadolinium compounds; Monocrystalline Iron Oxide Nanocompounds; Delivery of MRI Contrast Agents; MRI staining of the hippocampal system; Contrast Agents in Stem Cells Therapy; Thallium Autometallography; Targeting of Contrast Agents to Alzheimer’s disease Amyloid Plaques; References
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